Preliminary assessment of the accuracy of cutaneous T-cell lymphoma diagnosis through deep sequencing of the TRG gene.

Abstract

Background: The diagnostic challenges in early mycosis fungoides (MF) and other cutaneous T-cell lymphomas (CTCLs) persist despite advancements in molecular methods.

Objectives: To provide a preliminary assessment of next-generation sequencing (NGS) in analysing TRG (T-cell receptor gamma locus) sequences for distinguishing CTCLs from benign inflammatory skin disorders.

Methods: NGS was used to assess TRG sequences in skin samples from clinicopathologically proven CTCLs and benign inflammatory skin disorders.

Results: Our study analysed skin samples from a total of 36 participants, comprising 22 cases of CTCL, including 14 MF and 8 other CTCLs, alongside 14 cases of benign inflammatory skin disorders. According to LymphoTrack® criteria, monoclonality was detected in 16 (73%) of the 22 patients with CTCL. Specifically, in cases of MF, 10 of 14 (71%) were identified as monoclonal, with all 4 non-monoclonal cases being in the patch stage. For the other cases of CTCL, six of eight displayed monoclonality. Among the 22 patients with CTCL, 10 (45%) had multiple biopsies, with 8 (36%) displaying the same dominant clone across different sites. Among the 14 benign cases, only the case of erythrodermic psoriasis exhibited monoclonality. Our decision tree analysis suggests that a high frequency of the most abundant clone, its ratio to the third most abundant clone and TRG VγI segment usage are effective markers that can help in the diagnosis of CTCL.

Conclusions: A combination of the clone frequencies and TRG V segment usage may enhance diagnosis of MF and other CTCLs, helping to differentiate them from benign conditions. However, molecular diagnosis for patch-stage MF remains challenging.